Ventilator Strategies and Rescue Therapies for

PULMONARY/REVIEW ARTICLE
Ventilator Strategies and Rescue Therapies for Management of
Acute Respiratory Failure in the Emergency Department
Jarrod M. Mosier, MD*; Cameron Hypes, MD, MPH; Raj Joshi, MD; Sage Whitmore, MD; Sairam Parthasarathy, MD;
Charles B. Cairns, MD
*Corresponding Author. E-mail: [email protected], Twitter: @jarrodmosier.
Acute respiratory failure is commonly encountered in the emergency department (ED), and early treatment can have effects
on long-term outcome. Noninvasive ventilation is commonly used for patients with respiratory failure and has been
demonstrated to improve outcomes in acute exacerbations of chronic obstructive lung disease and congestive heart failure,
but should be used carefully, if at all, in the management of asthma, pneumonia, and acute respiratory distress syndrome.
Lung-protective tidal volumes should be used for all patients receiving mechanical ventilation, and FiO2 should be reduced
after intubation to achieve a goal of less than 60%. For refractory hypoxemia, new rescue therapies have emerged to help
improve the oxygenation, and in some cases mortality, and should be considered in ED patients when necessary, as
deferring until ICU admission may be deleterious. This review article summarizes the pathophysiology of acute respiratory
failure, management options, and rescue therapies including airway pressure release ventilation, continuous neuromuscular
blockade, inhaled nitric oxide, and extracorporeal membrane oxygenation. [Ann Emerg Med. 2015;-:1-13.]
Please see page XX for the Editor’s Capsule Summary of this article.
0196-0644/$-see front matter
Copyright © 2015 by the American College of Emergency Physicians.
http://dx.doi.org/10.1016/j.annemergmed.2015.04.030
INTRODUCTION
Acute respiratory failure is commonly encountered in
critically ill patients in the emergency department (ED).
Annually, there are nearly 1.5 million ED visits for acute
exacerbations of chronic obstructive pulmonary disease,1
2 million for acute asthma exacerbations,2 more than 1
million hospitalizations for acute cardiogenic pulmonary
edema,3,4 and nearly 200,000 admissions for acute lung
injury or acute respiratory distress syndrome.5 Recently, the
emergence of the H1N1 strain of influenza has led to many
patients’ presenting to the ED with acute respiratory
distress syndrome and refractory hypoxemia.6,7 Although
acute respiratory failure is common in the ED, the
expedient and proper management is both complex and
critically important. A recent multicenter observation study
showed that a concerning number of patients receive
suboptimal mechanical ventilation while in the ED.8 The
goals of the ED management of acute respiratory failure
include minimizing work of breathing, appropriately using
noninvasive positive-pressure ventilation (NIPPV),
improving gas exchange, optimizing patient-ventilator
synchrony, and limiting risk of ventilator-induced lung
injury. Controversy remains about the role of noninvasive
ventilation, timing of intubation, pharmacologic and
nonpharmacologic rescue therapies and their role in the
ED, and the role of extracorporeal membrane oxygenation
Volume
-,
no.
-
:
-
2015
(ECMO). This review will describe the pathophysiology
and state-of-the art treatment of acute respiratory failure
while stressing that many of these therapies should be
considered for patients in the ED rather than deferred
as ICU management, particularly for boarded patients
awaiting bed placement. Many of the treatment modalities
highlighted present targets for high-priority research
needs because they pertain to ED management of acute
respiratory failure. Figure 1 summarizes the invasive and
noninvasive ventilator management strategies for critically
ill ED patients with acute respiratory failure.
FOUNDATIONAL CONCEPTS
Work of Breathing
The 2 goals of respiration (eliminating carbon dioxide
[CO2] and supplying oxygen) require work. Work of
breathing is required by the respiratory muscles to
overcome resistive and elastic forces within the lung and
chest wall to move air and enable gas exchange. Resistive
work of breathing is the work required to overcome
resistance to airflow, whereas elastic work of breathing is
that which overcomes the lung’s desire to remain at
functional residual capacity. The total work of breathing is
the work per breath (both resistive and elastic) multiplied
by the respiratory rate.
Annals of Emergency Medicine 1
Mosier et al
Ventilator Strategies for Acute Respiratory Failure
Editor’s Capsule Summary
What is already known on this topic
Patients with acute respiratory failure are often
initially treated in the emergency department (ED)
and may require interventions commonly provided in
the ICU.
What question this study addressed
This article reviews ventilatory and oxygenation
failure and emphasizes physiology-based
interventions in immediate management.
What this study adds to our knowledge
Acute respiratory failure treatment must minimize
work of breathing and improve gas exchange while
avoiding lung injury. Invasive mechanical ventilation,
neuromuscular blockade, and early consultation for
initiation of advanced rescue techniques are all
appropriate elements of ED management.
How this is relevant to clinical practice
Emergency physicians should understand the range
of treatment options for acute respiratory failure and
initiate needed advanced interventions as part of a
continuum of care for these often critically ill
patients.
Understanding the relationships contributing to work
of breathing is crucial in understanding why certain
conditions lead to respiratory failure, for example, shock
and chronic obstructive pulmonary disease, and may guide
the types and timing of therapeutic interventions in the ED
and ICU. Patients in shock have elevated work of breathing
because of high ventilatory demand and resultant
hyperpnea and tachypnea, which occur in the setting of
decreased respiratory muscle perfusion predisposing them
to diaphragm fatigue.9-13 Mechanical ventilation can
reduce this work of breathing and the high oxygen
consumption required to maintain it and as a result has
become a recommended therapy in shock, even in the
absence of primary pulmonary pathology. In chronic
obstructive pulmonary disease, work of breathing is
increased by an increase in airways resistance, and also by
the increased elastance caused by dynamic hyperinflation,
which occurs when the inhaled tidal volume exceeds the
volume that can be exhaled during expiration. This
inequality of volumes leads to the development of
auto–positive end-expiratory pressure (PEEP), which must
then be overcome during inhalation to create the necessary
pressure gradient for air to flow into the lung. Reduction
2 Annals of Emergency Medicine
of this elastic work of breathing is the mechanism for
improved outcomes observed with the use of NIPPV.
Non-Invasive Positive Pressure Ventilation
Given the benefits observed with improved work of
breathing and respiratory support, NIPPV use for acute
respiratory failure is increasing.14-16 The use of NIPPV is
well supported in the treatment of chronic obstructive
pulmonary disease exacerbations, decompensated congestive
heart failure, and in immunocompromised patients.17-26
However, current data about the use of NIPPV in acute
respiratory distress syndrome and pneumonia demonstrate
poor outcomes.15,27-38 Despite evidence to avoid NIPPV in
mixed respiratory failure,15,28-30,32,37,38 NIPPV is frequently
used in the ED for these conditions. In light of this evidence,
a recent Agency for Healthcare Research and Quality report
highlighted the lack of evidence to support NIPPV use for
respiratory failure not caused by chronic obstructive
pulmonary disease or congestive heart failure.28
Although NIPPV may decrease the need for intubation
in patients with respiratory failure regardless of cause,
intubation after failed NIPPV is associated with increased
mortality.14-16,26,30,32,33,36,37 Despite a reduced need
for intubation and decreased mortality when NIPPV is
used for acute respiratory failure as a result of chronic
obstructive pulmonary disease,15,26,36 NIPPV failure
requiring intubation is associated with higher odds of
mortality than in patients with chronic obstructive
pulmonary disease who are intubated primarily.14,16
Hypoxemic respiratory failure treated with NIPPV has a
high failure rate, requiring intubation in 30% to 84% of
cases,15,30,37-39 and worsened mortality.30,32 In a study of
patients with hematologic malignancy and acute lung
injury, NIPPV success decreased mortality, whereas NIPPV
failure carried a nearly 40% higher mortality.35 It is not
clear what portion of the mortality noted with delayed
intubation is attributable to initial patient selection, disease
progression, or intubation-related complications.40
A challenge in the ED is the real-time assessment of
criteria to predict the failure (or success) of a trial of
NIPPV to avoid intubation. Because of diminished
physiologic reserve in these critically ill patients,
intubation can be particularly risky and carries a high rate
of significant hypoxemia, hemodynamic deterioration,
and cardiac arrest.41-53 As such, there is interest in
limiting these risks by prolonging safe apnea time or
avoiding intubation altogether.54-56 Current studies have
yielded mixed results. Several studies of NIPPV for
hypoxemic respiratory failure in non–chronic obstructive
pulmonary disease cohorts demonstrated decreased
intubation rates or mortality rates,19-21,34,36,57,58
Volume
-,
no.
-
:
-
2015
Mosier et al
Ventilator Strategies for Acute Respiratory Failure
Figure 1. Invasive and noninvasive ventilator treatment strategies of respiratory failure. The Global Initiative for Chronic
Obstructive Lung Disease (GOLD) guidelines state that NIPPV is indicated for respiratory acidosis with a pH less than 7.35.62,63
Sinuff et al64 recommend NIPPV with a pH greater than 7.25, and the British Thoracic Society guidelines state NIPPV is
“particularly” indicated with a pH greater than 7.25.65 The American Thoracic Society guidelines state that for patients with a
pH less than 7.25, NIPPV should be limited to the ICU for aggressive monitoring and immediate intubation if necessary.66 In
accordance with these guidelines and our clinical experience, we recommend a trial of NIPPV in the absence of contraindications
for a pH greater than 7.05. COPD, Chronic obstructive pulmonary disease; ARDS, acute respiratory distress syndrome; PPV, positivepressure ventilation; RR, respiratory rate; PF, PaO2/FiO2; APRV, airway pressure release ventilation; iNO, inhaled nitric oxide.
whereas others reported no improvement in these
parameters.31,59,60 There are some reports of success with
NIPPV use for the treatment of hypoxemic respiratory
failure caused by H1N1 influenza; however, there is a
high failure rate requiring intubation in a substantial
proportion (z50%).61 In multiple studies, the degree of
hypoxemia and the presence of pneumonia are strongly
associated with NIPPV failure.30,61,67-70 Severe
community-acquired pneumonia and acute respiratory
distress syndrome have been shown to portend NIPPV
failure, with a rate of more than 50%.71,72 NIPPV can be
useful for preoxygenating these patients with shunt
physiology54 before intubation and may avoid intubation
altogether; however, a trial of NIPPV for hypoxemic
Volume
-,
no.
-
:
-
2015
respiratory failure longer than 1 to 2 hours without
significant improvement is unlikely to be beneficial and
would possibly be harmful.29,33 Thus, the emergency
physician should be mindful of patient selection, and
diligent with monitoring and frequent evaluations, and
should intervene early if necessary when NIPPV is used.
VENTILATORY FAILURE
Physiology
Ventilatory failure occurs when minute ventilation
(minute ventilation¼respiratory ratetidal volume) is
no longer adequate to remove carbon dioxide from the
circulation; arterial CO2 [PaCO2]) increases and pH begins
to decrease. This may be due to either hypercapnic
Annals of Emergency Medicine 3
Ventilator Strategies for Acute Respiratory Failure
Mosier et al
Table 1. Causes of hypercapnic respiratory failure.
Recommendations for Emergency Department
Management
Patients with ventilatory failure as a result of chronic
obstructive pulmonary disease or asthma can receive a
trial of NIPPV in the absence of contraindications,
which include inability to protect the airway, vomiting,
hemodynamic instability, excessive secretions, or inability
to tolerate accidental removal of NIPPV mask.75 NIPPV
improves work of breathing, improves symptoms, reduces
mortality, and lessens the need for intubation compared
with oxygen supplementation alone in patients with
chronic obstructive pulmonary disease. However, NIPPV
for asthma is more controversial and less rigorously studied.
NIPPV may reduce work of breathing and symptoms
in severe asthma, but regional hyperinflation caused by
mucous plugging and flow restriction caused by bronchospasm
in asthma increases the potential of pneumothorax.
Monitoring while the patient receives NIPPV includes
blood gas analysis with initiation of NIPPV and
frequently (every 1 to 2 hours) until stable. For patients
with chronic obstructive pulmonary disease without
hypoxemia, a venous blood gas can be used instead of an
arterial blood gas. If the PCO2 is not improving or work
of breathing remains high (tachypnea or accessory muscle
use), the inspiratory pressure support should be increased
by 5 cm H2O until 20 cm H2O/5 cm H2O. Indications
for intubation include persistently high work of breathing
with evidence of fatigue or impending respiratory or
cardiac arrest, persistent hypoxemia, and failure to
improve while receiving NIPPV.
Invasive mechanical ventilation for chronic obstructive
pulmonary disease and asthma can be performed with
either a pressure- or volume-targeted mode. The critical
actions are to limit mean airway pressures and minute
ventilation to limit air trapping while allowing permissive
hypercapnia as long as the pH remains above 7.20 and the
patient is hemodynamically stable. For the emergency
physician, this may be easiest with a volume-targeted
mode (ie, assist control or pressure-regulated volume
control) with a low respiratory rate (10 to 12 breaths/min)
and may require a neuromuscular blocker. The respiratory
rate should be decreased until the expiratory flow
waveform returns to baseline before the next breath. If the
peak pressure alarms, evaluate the expiratory flow
waveform for air trapping and increase expiratory time by
decreasing the ventilator respiratory rate as needed
(Figure 2). If no air trapping is present, perform an
inspiratory pause to evaluate plateau pressure. If the
plateau pressure is greater than 30 cm H2O, a portable
radiograph or bedside ultrasound should be performed to
evaluate for pneumothorax. If no pneumothorax is
Causes of Hypercapnia
Decreased respiratory drive
Neuromuscular weakness
Chest wall mechanical defect
Increased dead space ventilation
Increased carbon dioxide load
Examples
Opiate or sedative overdose
Primary CNS injury
Spinal cord injury
Guillain-Barré syndrome
Myasthenia gravis
Electrolyte abnormalities
Severe fatigue
Chest wall trauma
Massive ascites
Massive pleural effusion
Emphysema
ARDS
Pulmonary embolism
Shock
Severe sepsis
Malignant hyperthermia
CNS, Central nervous system.
respiratory failure (type 2) or increased carbon dioxide
production that outstrips ventilatory capacity, such as
observed in shock (type 4 respiratory failure). Table 1
summarizes important causes of hypercapnic respiratory
failure.
A portion of every breath, known as dead space, never
reaches the alveolar-capillary interface and thus does not
participate in gas exchange.73 Increased dead space occurs
from any volume increase in conducting airways (eg,
emphysema) or a relative decrease in blood supply to the
alveoli (eg, pulmonary embolism). Thus, only alveolar
ventilation (alveolar ventilation¼[minute ventilation–dead
space]) participates in carbon dioxide removal, and any
increase in dead space or decrease in minute ventilation will
lead to decreased alveolar ventilation and a decrease in pH.11
Unlike oxygen, which is mostly transported bound to
hemoglobin, carbon dioxide produced in the periphery
freely dissolves across cell membranes into the blood. Thus,
for any increase in carbon dioxide production without a
change in alveolar ventilation, there is an equivalent
increase in PaCO2. With an increase in carbon dioxide
production, there must be an increase in alveolar
ventilation to maintain a neutral pH. Yet, although the
relationship between carbon dioxide production and
PaCO2 is linear, the relationship between PaCO2 and
alveolar ventilation is not. At normal alveolar ventilation
and below, the relationship is linear, meaning that
respiratory acidosis can be improved by increasing alveolar
ventilation in the same proportion. However, at
supranormal ranges of alveolar ventilation, carbon dioxide
removal plateaus, such that severe metabolic acidosis can
result in a respiratory compensation requirement that
cannot be met by increasing alveolar ventilation.73,74
4 Annals of Emergency Medicine
Volume
-,
no.
-
:
-
2015
Mosier et al
Ventilator Strategies for Acute Respiratory Failure
Figure 2. Expiratory flow, inspiratory, and expiratory holds for air trapping and auto-PEEP. Pressure (upper) and flow (lower)
ventilator waveforms during 3 consecutive breaths. An inspiratory hold maneuver (1) on the ventilator will stop all flow after
inspiration, isolating the pressure at the alveolar level known as plateau pressure. An expiratory hold maneuver (2) will inhibit
inspiration and measure the end-expiratory pressure in the respiratory system. Any elevation of the total PEEP above the set PEEP is
due to auto-PEEP. The flow waveform (lower) is useful for evaluating air trapping. After the first breath, the expiratory flow limb
returns to baseline before the next breath. After the second breath, the expiratory flow limb fails to return to baseline before the next
breath, leading to air trapping (3), as is commonly observed in obstructive lung disease such as asthma and chronic obstructive
lung disease.
present, perform an expiratory pause to evaluate autoPEEP. If auto-PEEP is elevated, then decrease the
respiratory rate, increase the inspiratory flow to lengthen
the expiratory time, or, in the case of chronic obstructive
pulmonary disease, increase set PEEP to 80% of the total
PEEP (set PEEP plus auto-PEEP) to assist respiratory
muscles in overcoming the auto-PEEP (Figure 2). If the
patient is hypotensive, disconnect the ventilator from the
endotracheal tube and externally compress the chest to
facilitate exhalation.
Volume
-,
no.
-
:
-
2015
Given the modern focus on lung-protective ventilation
with low tidal volumes, manipulation of the respiratory rate
has become the primary means of adjusting ventilation. As
respiratory rate increases, the proportion of time spent in
exhalation decreases. In this way, rapid respiratory rates
increase the risk of dynamic hyperinflation, in which more
air enters during inspiration than leaves in expiration. This
condition results in progressively higher intrathoracic
pressures, elevated peak and plateau pressures, an increase
in inspiratory threshold pressure required to trigger the
Annals of Emergency Medicine 5
Mosier et al
Ventilator Strategies for Acute Respiratory Failure
ventilator, and ultimately hemodynamic compromise as
intrathoracic pressure impairs venous return to the heart. In
certain circumstances, such as acute respiratory distress
syndrome and obstructive lung disease, efforts to maintain
eucapnia should be abandoned because attempts to
normalize ventilation may be damaging. This paradigm is
known as permissive hypercapnia, and the associated
acidemia is well tolerated down to at least a pH of 7.2, with
the exception of only a few types of patients (Figure 3).76
In special circumstances, the utmost effort must be made to
satisfy ventilatory demands, such as in the case of severe
metabolic acidosis (eg, diabetic ketoacidosis, salicylate
toxicity), to prevent loss of respiratory compensation and
cardiovascular collapse associated with a sudden decrease in
an already severely low pH. In these cases, an interesting
consideration is that even abandoning low tidal volume
ventilation and setting the respiratory rate as high as the
ventilator will allow may still be insufficient to match the
patient’s preintubation minute ventilation. Pressure
support (or “spontaneous”) mode ventilation with adequate
pressure support may be a useful alternative in the
nonparalyzed patient in these instances.
OXYGENATION FAILURE
Physiology
Hypoxemic (type 1) respiratory failure occurs from any
disturbance that leads to a decrease in dissolved oxygen
available in arterial blood (PaO2), which is required for
hemoglobin to bind oxygen for delivery to the cells. There
are 6 pathophysiologic mechanisms that lead to hypoxemia
(Table 2). The more common, clinically significant causes
of hypoxemic respiratory failure are ventilation-perfusion
(VQ) mismatch and shunt. Hypoxemia caused by
hypoventilation is a result of increased partial pressure of
carbon dioxide (PCO2) in the alveolar space displacing
oxygen.12 Diffusion abnormalities, such as interstitial lung
disease, typically cause clinically significant hypoxemia only
in increased demand states, such as high cardiac output.74
Figure 3. Contraindications to permissive hypercapnia.
6 Annals of Emergency Medicine
Table 2. Causes of hypoxemia.
Causes of Hypoxemia
VQ mismatch
Shunt physiology
Low available inspired oxygen
Hypoventilation
Diffusion defect
Low mixed venous oxygen
Examples
Pneumonia
ARDS
Pulmonary embolism
Cardiogenic pulmonary edema
Severe ARDS
Hepatopulmonary syndrome
Arteriovenous malformation
Intracardiac right-to-left shunt
High altitude
Scuba-diving mishap
Combustion within a closed space
Opiate overdose
COPD
Neuromuscular disease
Chest wall rigidity
Upper airway obstruction
Interstitial lung disease
Severe shock
Decreased FiO2 as a cause of hypoxemia is often a
misnomer that refers to a decrease in the partial pressure of
oxygen observed at high elevations because of barometric
pressure limitations on alveolar gases, given fixed fractions
of inspired oxygen, nitrogen, and water vapor.77 True
decreased FiO2 is exceptionally rare in the health care
setting and typically occurs in enclosed airtight spaces such
as spaceships or submarines, scuba-diving misadventures,
or massive fires where oxygen is rapidly consumed.
VQ mismatch, disruption of the optimal ratio of alveolar
ventilation to alveolar perfusion, leads to either
underperfused or underventilated alveoli (Figure 4). A high
VQ ratio occurs with underperfused alveoli relative to
ventilation and results in dead space ventilation, frequently
observed in chronic obstructive pulmonary disease as
emphysematous changes lead to parenchymal loss. A low
VQ ratio, or shunt physiology, occurs when perfused
alveolar units do not participate in gas exchange. Shunt
physiology may be either anatomic (eg, arteriovenous
malformation, intracardiac right-to-left shunting) or
physiologic because of alveolar filling (eg, cardiogenic or
noncardiogenic pulmonary edema) or increased flow in the
alveolar capillary bed (eg, hepatopulmonary syndrome). In
severe shock states with oxygen delivery-demand mismatch,
a low mixed venous oxygen saturation from low cardiac
output or high peripheral extraction can worsen arterial
hypoxemia in the presence of shunt physiology (eg, acute
respiratory distress syndrome).78
Acute respiratory distress syndrome is a life-threatening
cause of hypoxemic respiratory failure resulting from
either direct or indirect lung injury and represents a severe
form of VQ mismatch commonly encountered in the ED,
as exudative alveolar filling may lead to critical shunt
Volume
-,
no.
-
:
-
2015
Mosier et al
Ventilator Strategies for Acute Respiratory Failure
Figure 4. VQ mismatch versus shunt in ARDS. A, VQ mismatch occurs with regional differences in the optimal alveolar-capillary
interface as gas exchange occurs unimpeded (wide arrow) in some areas and restricted (narrow arrow) or prohibited (X) in others.
This mismatch can cause dead space when blood flow to well-ventilated alveoli is inhibited and areas of shunt where there is
alveolar filling or parenchymal loss; both are observed in patients with COPD who improve their VQ matching by hypoxic
vasoconstriction. B, Shunt occurs when blood flow does not participate in gas exchange, such as is observed with ARDS.
physiology.27,79 It was first identified in the early 1800s
and described in 1967,80 but it was not until 1994 that
the syndrome was formally defined to coordinate research
and epidemiologic efforts.27 The multisociety-sponsored
ARDS Definition Task Force convened in 2012 and
published the Berlin Definition of acute respiratory
distress syndrome in an attempt to increase precision of
the diagnosis (Table 3).79 Under the Berlin Definition,
nearly 80% of patients with acute respiratory distress
syndrome have profound oxygenation deficits (50%
moderate, 28% severe), which is associated with a high
mortality (32% for moderate, 45% for severe).79
Table 3. Berlin Definition of acute respiratory distress
syndrome.79
Timing
Within 1 wk of a known clinical insult or new or
worsening respiratory symptoms
Bilateral opacities not fully explained by effusions,
lobar/lung collapse, or nodules
Respiratory failure not fully explained by cardiac failure
or fluid overload. Need objective
assessment (ie, echocardiography) to exclude
hydrostatic edema if no risk factor present.
Chest imaging
Origin of edema
Oxygenation
Mild
200 mg Hg<PaO2/FiO2<300 mm Hg with PEEP or
CPAP >5 cm H2O
100 mg Hg<PaO2/FiO2<200 mm Hg with PEEP
>5 cm H2O
PaO2/FiO2 <100 mm Hg with PEEP >5 cm H2O
Moderate
Severe
Volume
-,
no.
-
:
-
2015
Additionally, nearly a third of patients with mild acute
respiratory distress syndrome progress to either moderate
or severe disease within a week, increasing the mortality to
nearly 50%.
The management of patients with acute respiratory
distress syndrome is challenging, and most patients require
mechanical ventilation. The alveolar filling process leads
to an oxygenation defect that leaves relatively uninvolved
portions of the lung responsible for performing gas exchange.
With inspiration, the volume will be heterogeneously
distributed, with the uninvolved high-compliance regions of
the lung receiving a higher proportion of the volume. This
heterogeneous distribution leads to a cycle of overdistention
and collapse, causing ventilator-induced lung injury, further
perpetuating acute respiratory distress syndrome, systemic
inflammation, multiorgan failure, and death. As such, lungprotective ventilation using low tidal volumes (6 mL/kg
predicted body weight), limiting plateau pressures (<30 cm
H2O), and avoiding oxygen toxicity (FiO2 <0.6) by the
application of PEEP has become the standard of care and is
important for preventing acute respiratory distress syndrome
in patients intubated for acute respiratory failure.81,82
However, despite some success with these interventions,
the mortality remains high. Consequently, there has
been increased interest in rescue therapies to improve
oxygenation and mortality in severe acute respiratory
distress syndrome.
Annals of Emergency Medicine 7
Mosier et al
Ventilator Strategies for Acute Respiratory Failure
Rescue Oxygenation Strategies in Acute Respiratory
Distress Syndrome
Airway pressure release ventilation is an increasingly
popular ventilator mode aimed at improving oxygenation
in patients with severe airspace disease. It maintains a high
airway pressure (eg, 30 cm H2O for 3 to 4 seconds),
periodically releasing the pressure to a set PEEP for a short
duration (eg, 10 cm H2O for 0.5 to 1 second) to allow
ventilation. In this way, it is similar to inverse ratio pressure
control ventilation in improving alveolar recruitment by
increasing the mean airway pressure through spending a
greater proportion of the breath in inspiration. The benefits
of airway pressure release ventilation are the ability to
maintain spontaneous breathing and improve alveolar
recruitment. The risk of airway pressure release ventilation,
as with any pressure-targeted mode, is injurious tidal
volumes as lung compliance changes. As compliance
improves with resolving disease, tidal volumes may
increase, exceeding lung-protective volumes and resulting
in volutrauma. Similarly, tidal volumes will decrease in the
presence of worsening compliance and result in ineffective
ventilation. For this reason, tidal volumes in patients
receiving pressure-targeted modes such as airway pressure
release ventilation must be closely monitored. Airway
pressure release ventilation has been beneficial in patients
with acute respiratory distress syndrome from H1N1
and has been shown to prevent the development of acute
respiratory distress syndrome in high-risk trauma
patients.7,83-88
Continuous neuromuscular blockade has been proposed
as an adjunct therapy in acute respiratory distress syndrome
to improve patient-ventilator synchrony and chest wall
compliance, and to reduce ventilator-induced lung
injury. A large-scale randomized controlled trial of early
continuous neuromuscular blockade for 48 hours
demonstrated a mortality and duration of mechanical
ventilation benefit compared with that of a control group.89
Continuous neuromuscular blockade is not without risks,
including development of critical illness myopathy and
high sedative requirements, leading to delirium and longterm cognitive abnormalities.90-93
Inhaled nitric oxide is a pulmonary vasodilator that is
delivered to the well-ventilated portions of the lung and
dilates the surrounding vasculature, improving VQ
matching and oxygenation. Although it has been shown to
improve oxygenation94 and reduce oxidative stress,95,96 it
has not been shown to improve mortality in patients with
acute respiratory distress syndrome, regardless of severity.97
Prone positioning is a nonpharmacologic method of
improving oxygenation in patients with severe acute
respiratory distress syndrome. This facedown positioning
8 Annals of Emergency Medicine
improves VQ match by decreasing dependent atelectasis
and has improved oxygenation and mortality in patients
with severe acute respiratory distress syndrome.98-102 Prone
positioning can be performed on a standard hospital bed
without special equipment, but drawbacks include making
routine nursing tasks and procedures more challenging.
ECMO is a method of mechanically supporting systemic
oxygenation or cardiac output by removing venous blood
from a large cannula in a central vein, oxygenating and
removing carbon dioxide with a membrane lung, and
returning that oxygenated blood to the circulation. ECMO
in severe acute respiratory distress syndrome allows lungprotective ventilation by allowing rest ventilator settings
and externally controlling gas exchange.103 Although
previous trials had negative results, recent improvements in
membrane technology and catheter systems have led to
renewed interest.104 A multicenter randomized controlled
trial showed benefit in patients referred to an ECMO
center for “consideration of ECMO” compared with
standard therapy at the referring center.105 Moreover,
ECMO has been successfully used for rescue therapy in
patients with severe acute respiratory distress syndrome
caused by pandemic influenza.106,107 Although ECMO
allows extracorporeal gas exchange and lung-protective
ventilation, cannulation commonly leads to a systemic
inflammatory response because of cytokine release, requires
anticoagulation, has bleeding complications, requires
intensive nursing, and typically leads to long ICU stays.
A randomized controlled trial (the EOLIA Trial) is
currently under way, investigating early ECMO initiation
after 3 to 6 hours of optimal ventilator and adjunct therapy.
ECMO may be a useful rescue therapy in facilities with
equipment, intensivists, and surgeons skilled in the
cannulation and management of ECMO patients.104,108
For emergency physicians, it will be critical to better
define which patients would benefit from ECMO for
optimal timing and referral to ECMO-capable units.
Recommendations for Emergency Department
Management
The management of oxygenation failure depends on
the etiology. NIPPV improves work of breathing and
reduces symptoms, mortality, and need for intubation
and mechanical ventilation in patients with cardiogenic
pulmonary edema.23 PEEP provides benefit in cardiogenic
pulmonary edema by improving left ventricular
performance. However, inspiratory pressure support may
be desired if the patient has high work of breathing with
inspiration. Initial NIPPV settings should be positive
end-expiratory pressure (PEEP) 8 to 10 cm H2O and,
if used, an inspiratory pressure support of 12 to 15 cm
Volume
-,
no.
-
:
-
2015
Mosier et al
Ventilator Strategies for Acute Respiratory Failure
H2O. If work of breathing remains high (tachypnea or
accessory muscle use) or there is persistent hypoxemia,
titrate PEEP up to 15 cm H2O. If no improvement is
noted, consider intubation. If NIPPV is used for
hypoxemic respiratory failure caused by pneumonia or
acute respiratory distress syndrome, it should be used
cautiously, given the high risk of failure and poor
outcomes in patients who fail treatment; and very close
observation is required to monitor response to therapy. If
requiring PEEP greater than 10 cm H2O or FiO2 greater
than 0.60, and PaO2 <100 mm Hg or PaO2:FiO2 ratio
less than 200 (ie, moderate or severe acute respiratory
distress syndrome according to the Berlin Definition) by 2
hours after initiation, intubation and mechanical
ventilation is recommended.
Invasive mechanical ventilation for hypoxemic
respiratory failure should be performed with a volumetargeted mode (assist control, synchronized intermittent
mandatory ventilation, or pressure-regulated volume
control), with the following initial settings: rate of 12
to 15 breaths/min or more in the absence of auto-PEEP
(or higher in the face of high ventilatory demand such
as in severe metabolic acidosis), tidal volume of 6 mL/
kg predicted body weight, PEEP of 5 to 8 cm H2O,
and FiO2 of 100% on initiation, with a rapid wean
using pulse oximetry to a goal FiO2 less than 60% to
prevent oxygen toxicity. If requiring FiO2 greater
than 60%, increase PEEP by 5 cm H2O every 30
minutes, as outlined in the ARDSnet PEEP/FiO2
table (Table 4).109 If the patient is still persistently
hypoxemic at a PEEP of 15 cm H2O, treat as refractory
hypoxemia.
Refractory hypoxemia (PaO2 <60 mm Hg, PaO2/FiO2
<200 despite FiO2 >60% or PEEP 15 cm H2O) is a
critical problem encountered in many patients with acute
respiratory distress syndrome and carries a high mortality.
Many methods have been used to treat it, although
supporting data are mixed. We recommend the following
therapies in patients with acute respiratory distress
syndrome with refractory hypoxemia:
Consider airway pressure release ventilation, adjusting
the high and low pressures as compliance improves to
ensure lung-protective tidal volumes (predicted body
weight 6 mL/kg).
Optimize sedation and analgesia to minimize patientventilator dyssynchrony. If dyssynchrony persists despite
optimal sedation and attempts to optimize patient comfort
with the ventilator such as providing adequate inspiratory
flow, consider continuous neuromuscular-blocking agent
infusion. Cisatracurium (Nimbex) is the preferred
neuromuscular-blocking agent because it is eliminated by
Hofmann degradation and thus does not need dosing
adjustment in renal or hepatic insufficiency. This
intervention has been demonstrated to improve mortality.
Early prone positioning should be considered to
improve alveolar recruitment and zone 2 ventilation.
This intervention has been demonstrated to improve
mortality.
Inhaled nitric oxide at 10 parts per million can be
considered to improve VQ matching and oxygenation,
although this has not been convincingly demonstrated to
improve patient mortality.
Discuss with intensivist colleagues whether the patient
is a candidate for ECMO. Precise indications for this
therapy have yet to be well established.
CONCLUSION
Acute respiratory failure is a commonly encountered
emergency that is identified in 2 forms, type 1, or hypoxemic
respiratory failure, and type 2, or hypercapnic respiratory
failure. Work (energy) is required to accomplish both
oxygenation and ventilation, the 2 primary goals of
respiration. Work of breathing is determined by respiratory
rate, resistance to airflow, and the elastance of the respiratory
system. NIPPV has been demonstrated to improve outcomes
in acute exacerbations of chronic obstructive pulmonary
disease and congestive heart failure; however, it should be
used carefully, if at all, in the management of asthma,
pneumonia, and acute respiratory distress syndrome.
Invasive mechanical ventilation should generally be initiated
Table 4. ARDSnet PEEP/FiO2 tables.
A, Low PEEP.
FiO2
PEEP, cm H2O
0.30
5
B, High PEEP,
FiO2
PEEP, cm H2O
0.40
5
0.30
12
0.40
8
0.30
14
0.50
8
0.40
14
0.50
10
0.40
16
0.60
10
0.70
10
0.50
16
0.70
12
0.50
18
0.70
14
0.80
14
0.50–0.80
20
0.90
14
0.80
22
0.90
16
0.90
18
0.90
22
1.0
18–24
1.0
22–24
Above are FiO2 and PEEP levels suggested by the ARDSnet investigators for achieving lung-protective ventilation. For example, a patient requiring 80% FiO2 has a suggested PEEP
of 14 according to the low-PEEP table and 20 to 22 according to the high-PEEP table. Clinical outcomes were similar between higher and lower PEEP assignments109; however, in
patients with refractory hypoxemia, use of the high-PEEP table may improve oxygenation.
Volume
-,
no.
-
:
-
2015
Annals of Emergency Medicine 9
Mosier et al
Ventilator Strategies for Acute Respiratory Failure
with a volume control mode in the ED. Lung-protective tidal
volumes based on ideal body weight should be provided even
in the absence of acute respiratory distress syndrome, and
FiO2 should be reduced shortly after intubation to achieve a
goal of less than 60%. In the setting of ventilatory failure
caused by chronic obstructive pulmonary disease or asthma,
goals of invasive mechanical ventilation are to limit mean
airway pressures, increase expiratory time, and, for chronic
obstructive pulmonary disease, augment set PEEP to
improve work of breathing. In cases of refractory hypoxemia,
emergency physicians should consider rescue therapies such
as airway pressure release ventilation, neuromuscular
blockade, prone positioning, and inhaled nitric oxide;
finally, consultation for consideration of ECMO may
be appropriate. Consideration of these therapies provides
important research questions for the emergency
physician, such as (1) which patients are more likely to
be successfully treated with NIPPV?; (2) in hypoxemic
respiratory failure, which patients are mostly likely to
benefit and what is the optimal timing and order of
the rescue therapies available such as neuromuscular
blockade, inhaled nitric oxide, and airway pressure release
ventilation?; and (3) which patients would benefit and
what is the optimal timing of ECMO initiation for severe
acute respiratory distress syndrome with refractory
hypoxemia?
The management of acute respiratory failure is a critical
and common aspect of emergency medicine. A keen
understanding of the underlying pathophysiology will serve
the emergency physician well in the management of acute
respiratory failure.
Supervising editor: Allan B. Wolfson, MD
Author affiliations: From the Division of Pulmonary, Critical Care,
Allergy and Sleep, Department of Medicine (Mosier, Hypes, Joshi,
Parthasarathy), and the Department of Emergency Medicine
(Mosier, Hypes, Joshi, Cairns), University of Arizona, Tucson, AZ;
and the Division of Emergency Critical Care, Department of
Emergency Medicine, University of Michigan Health System, Ann
Arbor, MI (Whitmore).
Funding and support: By Annals policy, all authors are required to
disclose any and all commercial, financial, and other relationships
in any way related to the subject of this article as per ICMJE conflict
of interest guidelines (see www.icmje.org). The authors have stated
that no such relationships exist and provided the following details:
Dr. Parthasarathy reports receiving grants from the National
Institutes of Health (NIH)/National Heart Lung and Blood Institute
(NHLBI), the Patient Centered Outcomes Research Institute, the
US Department of Defense, NIH National Cancer Institute, the
US Department of Army, the Johrei Institute, Younes Sleep
Technologies, Ltd., Niveus Medical Inc., and Philips-Respironics,
Inc.; personal fees from the American Academy of Sleep Medicine,
the American College of Chest Physicians, USMLEWorld Inc.,
10 Annals of Emergency Medicine
UpToDate Inc., and Philips-Respironics, Inc. outside the submitted
study; and nonfinancial support from the National Center for Sleep
Disorders Research of the NIH (NHLBI). In addition, Dr.
Parthasarathy holds patent UA 14-018 U.S.S.N. 61/884,654; PTAS
502570970 is pending. The above mentioned conflicts including
the patent are unrelated to the topic of this article. Dr. Cairns has
served as a consultant to bioMerieux and Teva in a capacity
unrelated to the topic of this article.
Publication dates: Received for publication March 7, 2015.
Revisions received March 31, 2015, and April 8, 2015. Accepted
for publication April 20, 2015.
REFERENCES
1. Hasegawa K, Tsugawa Y, Camargo CA Jr, et al. Frequent utilization of
the emergency department for acute heart failure syndrome: a
population-based study. Circ Cardiovasc Qual Outcomes. 2014;7:
735-742.
2. Schatz M, Kazzi AA, Brenner B, et al. Joint task force report:
supplemental recommendations for the management and follow-up
of asthma exacerbations. Introduction. J Allergy Clin Immunol.
2009;124:S1-S4.
3. Gray A, Goodacre S, Newby DE, et al. Noninvasive ventilation in acute
cardiogenic pulmonary edema. N Engl J Med. 2008;359:142-151.
4. Johnson JM. Management of acute cardiogenic pulmonary edema: a
literature review. Adv Emerg Nurs J. 2009;31:36-43.
5. Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes
of acute lung injury. N Engl J Med. 2005;353:1685-1693.
6. Napolitano LM, Angus DC, Uyeki TM. Critically ill patients with
influenza A(H1N1)pdm09 virus infection in 2014. JAMA. 2014;311:
1289-1290.
7. Sundar KM, Thaut P, Nielsen DB, et al. Clinical course of ICU patients
with severe pandemic 2009 influenza A (H1N1) pneumonia: single
center experience with proning and pressure release ventilation.
J Intensive Care Med. 2012;27:184-190.
8. Fuller BM, Mohr NM, Miller CN, et al. Mechanical ventilation and
acute respiratory distress syndrome in the emergency department: a
multi-center, observational, prospective, cross-sectional study. Chest.
2015. Available at: http://dx.doi.org/10.1378/chest.14-2476.
9. Vesconi S, Rossi GP, Mascheroni D, et al. [Bronchoalveolar lavage in
acute respiratory insufficiency]. Minerva Anestesiol. 1988;54:
279-283.
10. Roussos C, Grassino A, Macklem PT. Inspiratory muscle fatigue and
acute respiratory failure. CMAJ. 1980;122:1375-1377.
11. Roussos C, Koutsoukou A. Respiratory failure. Eur Resp J Suppl.
2003;47:3s-14s.
12. Roussos C, Macklem PT. The respiratory muscles. N Engl J Med.
1982;307:786-797.
13. Ward ME, Magder SA, Hussain SN. Oxygen delivery-independent
effect of blood flow on diaphragm fatigue. Am Rev Respir Dis.
1992;145:1058-1063.
14. Chandra D, Stamm JA, Taylor B, et al. Outcomes of noninvasive
ventilation for acute exacerbations of chronic obstructive pulmonary
disease in the United States, 1998-2008. Am J Respir Crit Care Med.
2012;185:152-159.
15. Schnell D, Timsit JF, Darmon M, et al. Noninvasive mechanical
ventilation in acute respiratory failure: trends in use and outcomes.
Intensive Care Med. 2014;40:582-591.
16. Walkey AJ, Greiner MA, Heckbert SR, et al. Atrial fibrillation among
Medicare beneficiaries hospitalized with sepsis: incidence and risk
factors. Am Heart J. 2013;165:949-955.e3.
17. Bott J, Carroll MP, Conway JH, et al. Randomised controlled trial of
nasal ventilation in acute ventilatory failure due to chronic obstructive
airways disease. Lancet. 1993;341:1555-1557.
Volume
-,
no.
-
:
-
2015
Mosier et al
Ventilator Strategies for Acute Respiratory Failure
18. Brochard L, Mancebo J, Wysocki M, et al. Noninvasive ventilation for
acute exacerbations of chronic obstructive pulmonary disease.
N Engl J Med. 1995;333:817-822.
19. Girou E, Brun-Buisson C, Taille S, et al. Secular trends in nosocomial
infections and mortality associated with noninvasive ventilation in
patients with exacerbation of COPD and pulmonary edema. JAMA.
2003;290:2985-2991.
20. Hilbert G, Gruson D, Vargas F, et al. Noninvasive ventilation in
immunosuppressed patients with pulmonary infiltrates, fever, and
acute respiratory failure. N Engl J Med. 2001;344:481-487.
21. Liesching T, Kwok H, Hill NS. Acute applications of noninvasive
positive pressure ventilation. Chest. 2003;124:699-713.
22. Lightowler JV, Wedzicha JA, Elliott MW, et al. Non-invasive positive
pressure ventilation to treat respiratory failure resulting from
exacerbations of chronic obstructive pulmonary disease: Cochrane
systematic review and meta-analysis. BMJ. 2003;326:185.
23. Masip J, Betbese AJ, Paez J, et al. Non-invasive pressure support
ventilation versus conventional oxygen therapy in acute cardiogenic
pulmonary oedema: a randomised trial. Lancet. 2000;356:2126-2132.
24. Nava S, Carbone G, DiBattista N, et al. Noninvasive ventilation in
cardiogenic pulmonary edema: a multicenter randomized trial. Am J
Respir Crit Care Med. 2003;168:1432-1437.
25. Plant PK, Owen JL, Elliott MW. Early use of non-invasive ventilation for
acute exacerbations of chronic obstructive pulmonary disease on
general respiratory wards: a multicentre randomised controlled trial.
Lancet. 2000;355:1931-1935.
26. Kramer N, Meyer TJ, Meharg J, et al. Randomized, prospective trial of
noninvasive positive pressure ventilation in acute respiratory failure.
Am J Respir Crit Care Med. 1995;151:1799-1806.
27. Walkey AJ, Summer R, Ho V, et al. Acute respiratory distress
syndrome: epidemiology and management approaches. Clin
Epidemiol. 2012;4:159-169.
28. Williams JW, Cox CE, Hargett CW, et al. Noninvasive Positive-Pressure
Ventilation (NPPV) for Acute Respiratory Failure. Agency for
Healthcare Research and Quality; Rockville, MD: 2012. Available at:
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0047897/.
Accessed November 12, 2014.
29. Truwit JD, Bernard GR. Noninvasive ventilation—don’t push too hard.
N Engl J Med. 2004;350:2512-2515.
30. Carrillo A, Gonzalez-Diaz G, Ferrer M, et al. Non-invasive ventilation in
community-acquired pneumonia and severe acute respiratory failure.
Intensive Care Med. 2012;38:458-466.
31. Delclaux C, L’Her E, Alberti C, et al. Treatment of acute hypoxemic
nonhypercapnic respiratory insufficiency with continuous positive
airway pressure delivered by a face mask: a randomized controlled
trial. JAMA. 2000;284:2352-2360.
32. Demoule A, Girou E, Richard JC, et al. Benefits and risks of success or
failure of noninvasive ventilation. Intensive Care Med. 2006;32:
1756-1765.
33. Esteban A, Frutos-Vivar F, Ferguson ND, et al. Noninvasive positivepressure ventilation for respiratory failure after extubation. N Engl J
Med. 2004;350:2452-2460.
34. Ferrer M, Esquinas A, Leon M, et al. Noninvasive ventilation in severe
hypoxemic respiratory failure: a randomized clinical trial. Am J Respir
Crit Care Med. 2003;168:1438-1444.
35. Gristina GR, Antonelli M, Conti G, et al. Noninvasive versus invasive
ventilation for acute respiratory failure in patients with hematologic
malignancies: a 5-year multicenter observational survey. Crit Care
Med. 2011;39:2232-2239.
36. Keenan SP, Kernerman PD, Cook DJ, et al. Effect of noninvasive
positive pressure ventilation on mortality in patients admitted with
acute respiratory failure: a meta-analysis. Crit Care Med. 1997;25:
1685-1692.
37. Thille AW, Contou D, Fragnoli C, et al. Non-invasive ventilation for
acute hypoxemic respiratory failure: intubation rate and risk factors.
Crit Care. 2013;17:R269.
Volume
-,
no.
-
:
-
2015
38. Thille AW, Frat JP, Brun-Buisson C. Trends in use and benefits of noninvasive ventilation as first-line therapy in acute respiratory failure.
Intensive Care Med. 2014;40:1179-1180.
39. Antonelli M, Conti G, Esquinas A, et al. A multiple-center survey on
the use in clinical practice of noninvasive ventilation as a first-line
intervention for acute respiratory distress syndrome. Crit Care Med.
2007;35:18-25.
40. Mosier JM, Sakles JC, Whitmore SP, et al. Failed non-invasive positive
pressure ventilation is associated with an increased risk of
intubation-related complications. Ann Intensive Care. In press.
41. Benedetto WJ, Hess DR, Gettings E, et al. Urgent tracheal intubation
in general hospital units: an observational study. J Clin Anesth.
2007;19:20-24.
42. Gudzenko V, Bittner EA, Schmidt UH. Emergency airway
management. Respir Care. 2010;55:1026-1035.
43. Jaber S, Amraoui J, Lefrant JY, et al. Clinical practice and risk factors
for immediate complications of endotracheal intubation in the
intensive care unit: a prospective, multiple-center study. Crit Care
Med. 2006;34:2355-2361.
44. Mort TC. The incidence and risk factors for cardiac arrest during
emergency tracheal intubation: a justification for incorporating the ASA
guidelines in the remote location. J Clin Anesth. 2004;16:508-516.
45. Mort TC. Complications of emergency tracheal intubation: immediate
airway-related consequences: part II. J Intensive Care Med.
2007;22:208-215.
46. Reynolds SF, Heffner J. Airway management of the critically ill patient:
rapid-sequence intubation. Chest. 2005;127:1397-1412.
47. Schwartz DE, Matthay MA, Cohen NH. Death and other complications
of emergency airway management in critically ill adults. A prospective
investigation of 297 tracheal intubations. Anesthesiology. 1995;82:
367-376.
48. Hasegawa Y, Sato M, Igarashi A. [Comparison of the Parker flex-tip tube
with the standard tube for Airtraq intubation]. Masui. 2012;61:143-146.
49. Sakles J, Chiu S, Mosier J, et al. The importance of first pass success
when performing orotracheal intubation in the emergency
department. Acad Emerg Med. In press.
50. Cook TM, Woodall N, Harper J, et al. Major complications of airway
management in the UK: results of the Fourth National Audit Project of
the Royal College of Anaesthetists and the Difficult Airway Society.
Part 2: intensive care and emergency departments. Br J Anaesth.
2011;106:632-642.
51. Griesdale DE, Bosma TL, Kurth T, et al. Complications of endotracheal
intubation in the critically ill. Intensive Care Med. 2008;34:1835-1842.
52. Simpson GD, Ross MJ, McKeown DW, et al. Tracheal intubation in
the critically ill: a multi-centre national study of practice and
complications. Br J Anaesth. 2012;108:792-799.
53. Walz JM, Zayaruzny M, Heard SO. Airway management in critical
illness. Chest. 2007;131:608-620.
54. Baillard C, Fosse JP, Sebbane M, et al. Noninvasive ventilation
improves preoxygenation before intubation of hypoxic patients. Am J
Respir Crit Care Med. 2006;174:171-177.
55. Tang L, Li S, Huang S, et al. Desaturation following rapid sequence
induction using succinylcholine vs. rocuronium in overweight
patients. Acta Anaesthesiol Scand. 2011;55:203-208.
56. Weingart SD, Levitan RM. Preoxygenation and prevention of
desaturation during emergency airway management. Ann Emerg
Med. 2012;59:165-175.e1.
57. Antonelli M, Conti G, Rocco M, et al. A comparison of noninvasive positivepressure ventilation and conventional mechanical ventilation in patients
with acute respiratory failure. N Engl J Med. 1998;339:429-435.
58. Martin TJ, Hovis JD, Costantino JP, et al. A randomized, prospective
evaluation of noninvasive ventilation for acute respiratory failure. Am
J Respir Crit Care Med. 2000;161:807-813.
59. Keenan SP, Sinuff T, Cook DJ, et al. Does noninvasive positive
pressure ventilation improve outcome in acute hypoxemic respiratory
failure? a systematic review. Crit Care Med. 2004;32:2516-2523.
Annals of Emergency Medicine 11
Mosier et al
Ventilator Strategies for Acute Respiratory Failure
60. Wood KA, Lewis L, Von Harz B, et al. The use of noninvasive positive
pressure ventilation in the emergency department: results of a
randomized clinical trial. Chest. 1998;113:1339-1346.
61. Nicolini A, Tonveronachi E, Navalesi P, et al. Effectiveness and
predictors of success of noninvasive ventilation during H1N1
pandemics: a multicenter study. Minerva Anestesiol. 2012;78:
1333-1340.
62. Pauwels RA, Buist AS, Calverley PM, et al. Global strategy for the
diagnosis, management, and prevention of chronic obstructive
pulmonary disease. NHLBI/WHO Global Initiative for Chronic
Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir
Crit Care Med. 2001;163:1256-1276.
63. Global Strategy for the Diagnosis, Management and Prevention of
COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD)
2015. Available from: http://www.goldcopd.org/. Accessed February
22, 2015.
64. Sinuff T, Keenan SP. Clinical practice guideline for the use of
noninvasive positive pressure ventilation in COPD patients with acute
respiratory failure. J Crit Care. 2004;19:82-91.
65. British Thoracic Society Standards of Care C. Non-invasive ventilation
in acute respiratory failure. Thorax. 2002;57:192-211.
66. American Thoracic Society / European Respiratory Society Task
Force. Standards for the Diagnosis and Management of Patients with
COPD [Internet]. Version 1.2. New York: American Thoracic Society;
2004 [updated 2005 September 8]. Available from: http://www.
thoracic.org/go/copd. Accessed February 22, 2015.
67. Ambrosino N, Vitacca M, Rampulla C. Standards for rehabilitative
strategies in respiratory diseases. Monaldi Arch Chest Dis. 1995;50:
293-318.
68. Carron M, Freo U, Zorzi M, et al. Predictors of failure of noninvasive
ventilation in patients with severe community-acquired pneumonia.
J Crit Care. 2010;25:540.e9-540.e14.
69. Veyrac G, Huguenin H, Guillon B, et al. [Cerebral meningeal
hemorrhage and acute cerebral angiopathy associated with the taking
of phenylpropanolamine: a new case]. Therapie. 2001;56:323-327.
70. Rana S, Jenad H, Gay PC, et al. Failure of non-invasive ventilation in
patients with acute lung injury: observational cohort study. Crit Care.
2006;10:R79.
71. Antonelli M, Conti G, Moro ML, et al. Predictors of failure of
noninvasive positive pressure ventilation in patients with acute
hypoxemic respiratory failure: a multi-center study. Intensive Care
Med. 2001;27:1718-1728.
72. Diaz-Ravetllat V, Ferrer M, Gimferrer-Garolera JM, et al. Risk factors of
postoperative nosocomial pneumonia after resection of
bronchogenic carcinoma. Resp Med. 2012;106:1463-1471.
73. Vincent JL, Abraham E, Moore FA, et al. Texbook of Critical Care. 6th
ed. Philadelphia, PA. Elsevier; 2011.
74. Mason RJ, Broaddus VC, Martin TR, et al. Murray and Nadel’s
Textbook of Respiratory Medicine. 5th ed. Elsevier; 2010.
75. Penuelas O, Frutos-Vivar F, Esteban A. Noninvasive positivepressure ventilation in acute respiratory failure. CMAJ. 2007;177:
1211-1218.
76. Hickling KG, Henderson SJ, Jackson R. Low mortality associated with
low volume pressure limited ventilation with permissive hypercapnia
in severe adult respiratory distress syndrome. Intensive Care Med.
1990;16:372-377.
77. Grocott MP, Martin DS, Levett DZ, et al. Arterial blood gases and
oxygen content in climbers on Mount Everest. N Engl J Med.
2009;360:140-149.
78. Rossaint R, Hahn SM, Pappert D, et al. Influence of mixed venous
PO2 and inspired O2 fraction on intrapulmonary shunt in patients
with severe ARDS. J Appl Physiol. 1995;78:1531-1536.
79. Force ADT, Ranieri VM, Rubenfeld GD, et al. Acute respiratory distress
syndrome: the Berlin Definition. JAMA. 2012;307:2526-2533.
80. Ashbaugh DG, Bigelow DB, Petty TL, et al. Acute respiratory distress
in adults. Lancet. 1967;2:319-323.
12 Annals of Emergency Medicine
81. Fuller BM, Mohr NM, Dettmer M, et al. Mechanical ventilation and
acute lung injury in emergency department patients with severe
sepsis and septic shock: an observational study. Acad Emerg Med.
2013;20:659-669.
82. Kleinman SH, Triulzi DJ, Murphy EL, et al. The Leukocyte Antibody
Prevalence Study-II (LAPS-II): a retrospective cohort study of
transfusion-related acute lung injury in recipients of high-plasmavolume human leukocyte antigen antibody-positive or -negative
components. Transfusion. 2011;51:2078-2091.
83. Andrews PL, Shiber JR, Jaruga-Killeen E, et al. Early application of
airway pressure release ventilation may reduce mortality in high-risk
trauma patients: a systematic review of observational trauma ARDS
literature. J Trauma Acute Care Surg. 2013;75:635-641.
84. Emr B, Gatto LA, Roy S, et al. Airway pressure release ventilation
prevents ventilator-induced lung injury in normal lungs. JAMA Surg.
2013;148:1005-1012.
85. Roy S, Habashi N, Sadowitz B, et al. Early airway pressure release
ventilation prevents ARDS—a novel preventive approach to lung
injury. Shock. 2013;39:28-38.
86. Roy SK, Emr B, Sadowitz B, et al. Preemptive application of airway
pressure release ventilation prevents development of acute
respiratory distress syndrome in a rat traumatic hemorrhagic shock
model. Shock. 2013;40:210-216.
87. Ramsey CD, Funk D, Miller RR 3rd, et al. Ventilator management for
hypoxemic respiratory failure attributable to H1N1 novel swine origin
influenza virus. Crit Care Med. 2010;38:e58-e65.
88. Kawashima H, Go S, Nara S, et al. Extreme efficiency of airway
pressure release ventilation (APRV) in a patient suffering from acute
lung injury with pandemic influenza A (H1N1) 2009 and high
cytokines. Indian J Pediatr. 2011;78:348-350.
89. Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in
early acute respiratory distress syndrome. N Engl J Med. 2010;363:
1107-1116.
90. Adnet F, Dhissi G, Borron SW, et al. Complication profiles of adult
asthmatics requiring paralysis during mechanical ventilation.
Intensive Care Med. 2001;27:1729-1736.
91. Pandharipande P, Cotton BA, Shintani A, et al. Prevalence and risk
factors for development of delirium in surgical and trauma intensive
care unit patients. J Trauma. 2008;65:34-41.
92. Van Rompaey B, Schuurmans MJ, Shortridge-Baggett LM, et al. Risk
factors for intensive care delirium: a systematic review. Intensive Crit
Care Nurs. 2008;24:98-107.
93. Hopkins RO, Weaver LK, Collingridge D, et al. Two-year cognitive,
emotional, and quality-of-life outcomes in acute respiratory distress
syndrome. Am J Respir Crit Care Med. 2005;171:340-347.
94. Dzierba AL, Abel EE, Buckley MS, et al. A review of inhaled nitric oxide
and aerosolized epoprostenol in acute lung injury or acute respiratory
distress syndrome. Pharmacotherapy. 2014;34:279-290.
95. Fioretto JR, Campos FJ, Ronchi CF, et al. Effects of inhaled nitric oxide
on oxidative stress and histopathological and inflammatory lung
injury in a saline-lavaged rabbit model of acute lung injury. Respir
Care. 2012;57:273-281.
96. Ronchi CF, Ferreira AL, Campos FJ, et al. Interactive effects of
mechanical ventilation, inhaled nitric oxide and oxidative stress in
acute lung injury. Respir Physiol Neurobiol. 2014;190:118-123.
97. Adhikari NK, Dellinger RP, Lundin S, et al. Inhaled nitric oxide does
not reduce mortality in patients with acute respiratory distress
syndrome regardless of severity: systematic review and metaanalysis. Crit Care Med. 2014;42:404-412.
98. Sud S, Friedrich JO, Taccone P, et al. Prone ventilation reduces
mortality in patients with acute respiratory failure and severe
hypoxemia: systematic review and meta-analysis. Intensive Care
Med. 2010;36:585-599.
99. Guerin C, Reignier J, Richard JC, et al. Prone positioning in severe
acute respiratory distress syndrome. N Engl J Med. 2013;368:
2159-2168.
Volume
-,
no.
-
:
-
2015
Mosier et al
Ventilator Strategies for Acute Respiratory Failure
100. Beitler JR, Shaefi S, Montesi SB, et al. Prone positioning reduces
mortality from acute respiratory distress syndrome in the low tidal
volume era: a meta-analysis. Intensive Care Med. 2014;40:332-341.
101. Hu SL, He HL, Pan C, et al. The effect of prone positioning on mortality in
patients with acute respiratory distress syndrome: a meta-analysis of
randomized controlled trials. Crit Care. 2014;18:R109.
102. Sud S, Friedrich JO, Adhikari NK, et al. Effect of prone positioning
during mechanical ventilation on mortality among patients with acute
respiratory distress syndrome: a systematic review and metaanalysis. CMAJ. 2014;186:E81-E90.
103. Turner DA, Cheifetz IM. Extracorporeal membrane oxygenation for
adult respiratory failure. Respir Care. 2013;58:1038-1052.
104. Morris AH. Exciting new ECMO technology awaits compelling scientific
evidence for widespread use in adults with respiratory failure.
Intensive Care Med. 2012;38:186-188.
105. Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy and economic
assessment of conventional ventilatory support versus
Volume
-,
no.
-
:
-
2015
106.
107.
108.
109.
extracorporeal membrane oxygenation for severe adult respiratory
failure (CESAR): a multicentre randomised controlled trial. Lancet.
2009;374:1351-1363.
Noah MA, Peek GJ, Finney SJ, et al. Referral to an extracorporeal
membrane oxygenation center and mortality among patients
with severe 2009 influenza A(H1N1). JAMA. 2011;306:
1659-1668.
Davies A, Jones D, Bailey M, Beca J, et al; Australia and New Zealand
Extracorporeal Membrane Oxygenation Influenza I. Extracorporeal
membrane oxygenation for 2009 influenza A(H1N1) acute respiratory
distress syndrome. JAMA. 2009;302:1888-1895.
Zapol WM, Snider MT, Hill JD, et al. Extracorporeal membrane
oxygenation in severe acute respiratory failure. A randomized
prospective study. JAMA. 1979;242:2193-2196.
Brower RG, Lanken PN, MacIntyre N, et al. Higher versus lower
positive end-expiratory pressures in patients with the acute
respiratory distress syndrome. N Engl J Med. 2004;351:327-336.
Annals of Emergency Medicine 13